1. Field of the Invention
The present invention generally relates to instrumentation and techniques for monitoring blood clot properties.
2. Description of the Prior Art
The structural and mechanical properties of plasma clots are important for clot integrity and proper hemostasis. In my earlier U.S. Pat. No. 4,986,964, the complete contents of which is herein incorporated by reference, a technique and device was described which directly measures force development during platelet mediated clot retraction. Clot retraction is dependent on intact platelet membrane structure, normal platelet metabolic function, fibrin structure and normal platelet-fibrin interactions. While the physiologic role of clot retraction remains to be fully defined, changes in clot retraction are sensitive to a spectrum of both fluid phase and platelet abnormalities. Force development is completely dependent on platelet function and if platelet function is abnormal or if no platelets are present, force development will be reduced or completely absent.
While force development is dependent on platelet function, the degree of deformation of a blood clot is dependent in large measure on fibrin structure. If the clot structure is very rigid, as sometimes occurs in diseases such as multiple myeloma, clot deformation may be minimal even with large force development. The elastic modulus of a blood clot (gel) is a commonly used measurement of rigidity. For years, clinicians and investigators have been measuring gel elastic modulus as a screen of clot "integrity", meaning a determination of whether the blood possesses the structural characteristics necessary to impede and eventually stop the flow of blood at a site of injury.
There are currently two types of elastic modulus measurements currently being performed on blood clots: tensile (linear stretching) modulus and torsional (twisting) modulus. Tensile modulus measurement techniques for blood clots have been described in Ferry et al., J. Am. Chem. Soc. 69:388-400 (1947), Ferry, Adv. Protein Chem. 4:1-78 (1948), and Ferry et al., Arch. Biochem. 34:424 (1951). Clot tensile modulus measurements have typically been performed on cylindrical clots formed in and subsequently removed from clot forming chambers or vessels. Because manipulation of the clot is required for these types of measurements, there is a chance of inducing irreversible structural changes in the clot and, thereby altering, in unknown ways, the measured elastic modulus. Torsional modulus measurement techniques for blood clots have been described in U.S. Pat. No. 4,317,363 to Shen, and Carr and Shen et al., Analytical Biochem. 72:202-211 (1976). Measurement of clot torsional elastic modulus avoids clot manipulation by forming the clot directly within the vessel in which the measurement is made.
Elasticity measurements can be made on a spectrum of specimens ranging from purified solutions to plasma. Unfortunately, the interpretation of elastic modulus variations is difficult in complex systems. Changes in elastic modulus of clots made from purified protein solutions generally reflect changes in fibrin structure. In systems containing cellular elements such as erythrocytes and platelets, changes in elastic modulus may result from fibrin structural alteration or from altered cell function. Since elastic modulus is a complex function of multiple variables, the utility of an isolated elastic modulus measurement is limited. Thus, elastic modulus measurements have not been routinely performed on patient specimens.